The direct relationship between traditional CVD risk factors and risk of atherosclerosis is well established. Dietary modifications which lower blood pressure and lipids provide a likely explanation for much of the risk reduction. However, oxidative stress, including oxidation of LDL-c (oxLDL) appears to be an important, if not obligatory step in the pathogenesis of atherosclerosis and may accelerate this process which is marked by inflamation (Steinberg, 1989). Measurement of inflammation and oxidative stress using serum and urine biomarkers may offer insight into mechanisms of CVD risk reduction beyond that which is predicted by lipids or other CVD risk factors alone. In this application we propose to measure the effects of dietary patterns that vary the type (high and low glycemic index) and the amount of carbohydrate in the diet (high carbohydrate and low carbohydrate) on markers of inflammation and oxidative stress. This study will be conducted within the setting of the OMNI-CARB trial (Optimal Macronutrient Intake and Carbohydrates)- a randomized cross over trial of 160 adults with prehypertension or stage 1 hypertension enrolling participants between 2008 and 2011 at Johns Hopkins and Harvard. The applicant is a co-investigator and this application has the full support and approval of the Principal Investigator (Frank Sacks, Harvard University). The primary aim of the OMNI-CARB study is to address the efficacy, separate and combined, of reducing carbohydrate from a high level (58% kcal) to a low level (43% kcal) and of lowering the glycemic index from a high level (glycemic index>85) to a low level (glycemic index<55) on the major established diet-related CVD risk factors, as well as insulin sensitivity. Measurement of biomarkers reflective of oxidative stress and inflammation are particularly relevant outcomes in this trial since modifying the glycemic index within a fixed macronutrients diet (carbohydrate, protein and fats held constant) is expected to results in only modest effects on serum lipids and other traditional CVD risk factors (blood pressure). We hypothesize that consumption of a fixed "low carbohydrate diet" and "low glycemic index" diet will decrease oxidative stress and inflammation compared with consumption an isocaloric "high carbohydrate" diet and "high glycemic index" diet. PUBLIC HEALTH RELEVANCE: In this application we propose to measure the effects of dietary patterns that vary the type (high and low glycemic index) and the amount of carbohydrate in the diet (high carbohydrate and low carbohydrate) on markers of inflammation and oxidative stress. This study will be conducted within the setting of the OMNI-CARB trial (Optimal Macronutrient Intake and Carbohydrates)- a randomized cross over trial of 160 adults with prehypertension or stage 1 hypertension enrolling participants between 2008 and 2011 at Johns Hopkins and Harvard. We hypothesize that consumption of a fixed "low carbohydrate diet" and "low glycemic index" diet will decrease oxidative stress and inflammation compared with consumption an isocaloric "high carbohydrate" diet and "high glycemic index" diet. (End of Abstract)